Show simple item record

dc.contributor.authorWoolston, Aen_US
dc.contributor.authorKhan, Ken_US
dc.contributor.authorSpain, Gen_US
dc.contributor.authorBarber, LJen_US
dc.contributor.authorGriffiths, Ben_US
dc.contributor.authorGonzalez-Exposito, Ren_US
dc.contributor.authorHornsteiner, Len_US
dc.contributor.authorPunta, Men_US
dc.contributor.authorPatil, Yen_US
dc.contributor.authorNewey, Aen_US
dc.contributor.authorMansukhani, Sen_US
dc.contributor.authorDavies, MNen_US
dc.contributor.authorFurness, Aen_US
dc.contributor.authorSclafani, Fen_US
dc.contributor.authorPeckitt, Cen_US
dc.contributor.authorJiménez, Men_US
dc.contributor.authorKouvelakis, Ken_US
dc.contributor.authorRanftl, Ren_US
dc.contributor.authorBegum, Ren_US
dc.contributor.authorRana, Ien_US
dc.contributor.authorThomas, Jen_US
dc.contributor.authorBryant, Aen_US
dc.contributor.authorQuezada, Sen_US
dc.contributor.authorWotherspoon, Aen_US
dc.contributor.authorKhan, Nen_US
dc.contributor.authorFotiadis, Nen_US
dc.contributor.authorMarafioti, Ten_US
dc.contributor.authorPowles, Ten_US
dc.contributor.authorLise, Sen_US
dc.contributor.authorCalvo, Fen_US
dc.contributor.authorGuettler, Sen_US
dc.contributor.authorvon Loga, Ken_US
dc.contributor.authorRao, Sen_US
dc.contributor.authorWatkins, Den_US
dc.contributor.authorStarling, Nen_US
dc.contributor.authorChau, Ien_US
dc.contributor.authorSadanandam, Aen_US
dc.contributor.authorCunningham, Den_US
dc.contributor.authorGerlinger, Men_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2019-06-27T09:06:48Z
dc.date.issued2019-07-08en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/31287991en_US
dc.identifierS1535-6108(19)30255-7en_US
dc.identifier.citationCancer Cell, 2019, 36 (1), pp. 35 - 50.e9en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3276
dc.identifier.eissn1878-3686en_US
dc.identifier.doi10.1016/j.ccell.2019.05.013en_US
dc.description.abstractDespite biomarker stratification, the anti-EGFR antibody cetuximab is only effective against a subgroup of colorectal cancers (CRCs). This genomic and transcriptomic analysis of the cetuximab resistance landscape in 35 RAS wild-type CRCs identified associations of NF1 and non-canonical RAS/RAF aberrations with primary resistance and validated transcriptomic CRC subtypes as non-genetic predictors of benefit. Sixty-four percent of biopsies with acquired resistance harbored no genetic resistance drivers. Most of these had switched from a cetuximab-sensitive transcriptomic subtype at baseline to a fibroblast- and growth factor-rich subtype at progression. Fibroblast-supernatant conferred cetuximab resistance in vitro, confirming a major role for non-genetic resistance through stromal remodeling. Cetuximab treatment increased cytotoxic immune infiltrates and PD-L1 and LAG3 immune checkpoint expression, potentially providing opportunities to treat cetuximab-resistant CRCs with immunotherapy.en_US
dc.format.extent35 - 50.e9en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectEGFRen_US
dc.subjectcancer evolutionen_US
dc.subjectcancer genomicsen_US
dc.subjectcancer-associated fibroblastsen_US
dc.subjectcetuximaben_US
dc.subjectcolorectal canceren_US
dc.subjectdrug resistance mechanismsen_US
dc.subjectimmunotherapyen_US
dc.subjectmolecular subtypeen_US
dc.subjectpredictive biomarkeren_US
dc.titleGenomic and Transcriptomic Determinants of Therapy Resistance and Immune Landscape Evolution during Anti-EGFR Treatment in Colorectal Cancer.en_US
dc.typeJournal Article
dcterms.dateAccepted2019-05-23en_US
rioxxterms.versionofrecord10.1016/j.ccell.2019.05.013en_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2019-07-08en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfCancer Cellen_US
pubs.issue1en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Gastrointestinal Cancers Clinical Trials
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Gastrointestinal Cancers Clinical Trials/Gastrointestinal Cancers Clinical Trials (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Systems and Precision Cancer Medicine
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Oncogenomics
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume36en_US
pubs.embargo.termsNot knownen_US
icr.researchteamGastrointestinal Cancers Clinical Trialsen_US
icr.researchteamMedicine (RMH Smith Cunningham)en_US
icr.researchteamSystems and Precision Cancer Medicineen_US
icr.researchteamTranslational Oncogenomicsen_US
dc.contributor.icrauthorBarber, Louiseen_US
dc.contributor.icrauthorWoolston, Andrewen_US
dc.contributor.icrauthorPunta, Marcoen_US
dc.contributor.icrauthorNewey, Aliceen_US
dc.contributor.icrauthorLise, Stefanoen_US
dc.contributor.icrauthorStarling, Naureenen_US
dc.contributor.icrauthorChau, Ianen_US
dc.contributor.icrauthorSadanandam, Angurajen_US
dc.contributor.icrauthorCunningham, Daviden_US
dc.contributor.icrauthorGerlinger, Marcoen_US


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record

http://creativecommons.org/licenses/by/4.0/
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/